Dr. Resnick is a physicist committed to establishing a career in systems biology research and a research program designed to study cell signaling. His short-term career goals are to develop solid foundations in electrophysiological and immunostaining experimental techniques, protein function, cell biology and current medical practices. The proposed career development plan will train Dr. Resnick in 1) electrophysiological experimental techniques and immunofluorescent methods; 2) Cell biology, and the functional roles of cell signaling molecules; and 3) independent career development and translational research. Mentors at Case Western Reserve University (CWRU), and University Hospitals (UH) will provide training and expertise, and monitor and support Dr. Resnick's career advancement. The existing collaborative nature of this research and training environment is suited to the multi-disciplinary nature of the project and Dr. Resnick's career goals in biomedical research. The research plan will investigate the possible role of the primary cilium in renal epithelial cells as a mechanical sensor of the cell's external fluid environment, and the metabolic pathways that are regulated by that sensing mechanism. First, renal epithelial cells will be cultured and placed within a calibrated flow chamber, and their cilia monitored. Second, laser tweezers will be used to manipulate the cilia in a controlled fashion. Calcium imaging will be performed to determine the metabolic effects of cilia deformation. It is theorized that improper functioning of the cilia leads to polycystic kidney disease via improper regulation of angiotensin II; understanding and validating this model could lead to effective treatments by developing targeted drugs. This career development plan will establish Dr. Resnick as an independent investigator in biomedical research and prepare him to lead research efforts in the development of cell regulatory models.